The principal objective of this proposal is to determine how the alpha CaMKII modulates the plasticity of hippocampal neurons, and to investigate how these physiological mechanisms affect either hippocampal-dependent learning or memory. The key tools in these studies are transgenic mice with mutations on the alpha CaMKII and synapsin I. The specific aims are: 1. To determine how mutations in alpha CaMKII and in synapsin 1 affect post-tetanic potentiation (PTP) and paired- pulse facilitation (PPF); 2. To determine the impact of the Synapsin 1-/- and the alpha CaMKII+/- mutation on performance in water maze and fear conditioning tasks; 3. To determine whether the mutants studied in this proposal have deficits in other properties of associative learning and/or other general behavioral responses; 4. To derive and study an alpha CaMKII mutant mouse with a substitution of threonine-286 by alanine, and another mutant with a substitution of lysine 42 by methionine; 5. To determine whether the alpha CaMKII+/- mutation disrupts memory formation.